This is a resubmission of 2 R01 DA1282806, "Cognitive Neuropsychology of HIV and Drug Abuse," a program of theory driven researchdesigned to test the hypothesisthat HIV infection significantly increases vulnerability to neurobehavioral complications amongsubstance dependent-individuals (SDIs).We propose that certain neurocognitive deficits, such as abnormalities of inhibition and reward processing, will be present among both HIV+ and HIV- SDIs comparedwith persons with no history of drug dependence. Additionally, HIV+ SDIs will show deficits in nondeclarative learning and memory,functions dependent on the integrity of neostriatum, a subcortical region typically affectedprominently by HIV; HIV- SDIs are expectedto show some level of impairment in nondeclarative learning but of lesser severity comparedwith HIV+ SDIs. We propose to moveforwardwith the following primary goals: 1)we will compare HIV+ and matched HIV- SDIs on carefully chosen measuresof response inhibition, impulsive choice, and procedural learning; 2) we will recruit and test two control groups of HIV+ and HIV- personswith no history of drug dependence in order to address the potential unique and synergistic effects of a positive HIV serostatuswith a history of substance dependence; 3) we will examinethe association of these neurocognitive functions with indices of critical daily and social functions. 4) we will develop and pilot test an MRI protocolfor investigating structural brain integrity among HIV+ and HIV- persons with and without a history of substance dependence. Our model has considerable potential utility as a first step towardstudy of HIV-specific effects on brain function in the context of the more non-specific cognitive effects of drug dependence, an area in which research is lacking. The translational and public health relevance of these studies includes the potential for development of more effective clinical neuropsychological measures for assessment of HIV+ and HIV- SDIs; development of indices with relevance to employment, continued risk behavior and adherence with medication; predicting which cognitive deficits observed might be more likely to remit with abstinence from drugs; anddevelopment of a frameworkfor evaluating and perhaps distinguishing response to treatment of substance dependence among HIV+ and HIV-infected SDIs.